{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:35:51Z","timestamp":1777336551130,"version":"3.51.4"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":1996,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institute for Medical Research Development and Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran","award":["397180"],"award-info":[{"award-number":["397180"]}]},{"name":"National Institute for Medical Research Development and Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran","award":["397180"],"award-info":[{"award-number":["397180"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Current studies indicate that melatonin can counteract renin\u2013angiotensin\u2013aldosterone system and sympathetic over activity in heart failure (HF) and might have a protective and repairing effect on cardiovascular injuries, skeletal muscle weakness, and metabolic abnormalities, which are common pathological processes in patients with HF. The MeHR trial (Melatonin for Heart Failure with Reduced Ejection Fraction) aims to evaluate the effect of oral melatonin on myocardial, skeletal muscle, and metabolic dysfunctions in HF, which leads to lower quality of life and increased morbidity and mortality in these patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This is a double-blind randomized clinical trial with two parallel arms of 1:1 allocation, which recruits 90 outpatients with HF with reduced ejection fraction. Participants receive 10 mg tablets of melatonin or placebo for 24 weeks. The primary outcomes are changes in echocardiographic indexes of HF and serum levels of N terminal pro brain natriuretic peptide. Secondary outcome is a composite clinical endpoint score including all-cause mortality, hospitalization for HF, and change in the quality of life during the study. Other outcomes are the evaluation of melatonin attributable adverse effects, flow-mediated vasodilation, skeletal muscle mass, exercise capacity, and serum markers of inflammation, oxidative stress, and metabolism. Statistical analysis will include simple unadjusted analyses for the detection of differences between groups and changes in outcomes and also a generalized linear mixed model to explore potential associations between outcomes and participant characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results of this comprehensive study might elucidate the safety of oral melatonin in patients with HF and provide some evidence on its effectiveness as an adjunctive therapy to enhance the well-being of these patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12829","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T01:21:00Z","timestamp":1593739260000},"page":"3142-3150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Effect of Melatonin on Heart Failure: Design for a Double-Blinded Randomized Clinical Trial"],"prefix":"10.1093","volume":"7","author":[{"given":"Masoumeh","family":"Sadeghi","sequence":"first","affiliation":[{"name":"Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences , Isfahan ,","place":["Iran"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeid","family":"Khosrawi","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, School of Medicine, Isfahan University of Medical Sciences , Isfahan ,","place":["Iran"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyan","family":"Heshmat-Ghahdarijani","sequence":"additional","affiliation":[{"name":"Heart Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences , Isfahan ,","place":["Iran"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yousof","family":"Gheisari","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Research Center, Isfahan University of Medical Sciences , Isfahan ,","place":["Iran"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamidreza","family":"Roohafza","sequence":"additional","affiliation":[{"name":"Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences , Isfahan ,","place":["Iran"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjan","family":"Mansoorian","sequence":"additional","affiliation":[{"name":"Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences , Isfahan ,","place":["Iran"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shervin Ghaffari","family":"Hoseini*","sequence":"additional","affiliation":[{"name":"Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences , Isfahan ,","place":["Iran"]},{"name":"Department of Physical Medicine and Rehabilitation, School of Medicine, Isfahan University of Medical Sciences , Isfahan ,","place":["Iran"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"2026012114055099600_ehf212829-bib-0001","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). 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